Magnetic resonance imaging (MRI) relies on the relaxation properties of excited hydrogen nuclei in water and lipids to create images. When the target object to be imaged is placed in a uniform magnetic field, the forces in the magnetic field cause the spins of atomic nuclei having a non-zero spin to align in a particular manner with the applied magnetic field. By way of example, hydrogen atoms have a simple spin (1/2) and therefore align either parallel or anti-parallel to the magnetic field. A radio frequency pulse (RF) is then applied in a direction perpendicular to the magnetic field and removed. When the RF signal is removed, the atomic nuclei relax. During the relaxation process, the nuclei release energy by emitting an RF signal unique to the nuclei, which may be measured by a conductive field coil placed around the target object. This measurement is processed or reconstructed to obtain the magnetic resonance images.
The signal intensity of a given tissue type depends upon the density of the protons in the tissue. However, the contrast of the image also depends on two other tissue-specific parameters: the longitudinal relaxation time (T1) and the transverse relaxation time (T2). T1 defines the time required for the displaced nuclei to return to equilibrium, that is to say, the time required for the nuclei to realign themselves in the magnetic field. T2 is the time required for the signal emitted by a specific tissue type to decay.
Image contrast is created by using a selection of image acquisition parameters that weights signals by T1, T2 or T2*, or no relaxation time, which are known in the art as proton density images. For example, in the brain, T1-weighting causes the nerve connections of white matter to appear white, and the congregations of neurons of gray matter to appear gray. Cerebrospinal fluid appears dark.
Dynamic Susceptibility Contrast (DSC) MRI and Dynamic Contrast Enhanced (DCE) MRI are two minimally-invasive imaging techniques frequently employed to probe the angiogenic activity of brain neoplasms based on estimates of vascularity and vascular permeability. Contrast agents may be used to enhance tissue contrast in MRI images by inducing susceptibility contrast effects when injected. Most commonly, a paramagnetic contrast agent, typically a gadolinium compound is employed for this purpose; although, as will be discussed in greater detail below, several different contrast agents may also be used. Gadolinium-enhanced tissues and fluids appear extremely bright in T1-weighted images, thereby providing high contrast sensitivity which facilitates the detection of vascular issues (tumors) and permits assessment of brain perfusion, such as that which occurs following a stroke. Cerebral blood volume (CBV) and cerebral blood flow (CBF) can be measured, and other hemodynamic and vascular parameters can be derived from these measurements. However, a significant problem associated with the use of gadolinium-based contrast agents is that they leave or leak from the blood vessels. This leakage results in undesirable T1 and T2 relaxation effects that confound the measurement of perfusion.
Efforts to correct contrast leakage effects on measurements for rCBV are discussed in U.S. Pat. No. 6,807,441 B2 issued on Oct. 19, 2004, and in U.S. Patent Application Publication No. US2006/0034765 A1 published on Feb. 16, 2006. These disclosures entail the use of gradient-echo and spin-echo NMR signals and either a ΔR2 weighing ratio or the T2* and T2 relaxation rates to measure tumor angiogenesis.
However, the results of both DSC- and DCE-MRI may be confounded by the opposing effects of gadolinium. While necessary for the DCE-MRI technique, the shift in compartmental distribution of the contrast agent from the intravascular space to the EES results in T1 shortening effects that compete with the susceptibility-induced signal dropout, which can confound DSC-MRI signal time courses. The most well characterized DSC-MRI parameter affected by T1 leakage effects is rCBV.
Accordingly, a need exists for a method of measure and assessing the hemodynamic properties of a tumor where extravasation of a contrast agent is present, not only in brain tumors where the blood-brain barrier may be disrupted by disease, but also in tumors present in other parts of the body where extravasation may be present.